Methods and Compositions for Determining a Graft Tolerant Phenotype in a Subject

Abstract

Methods are provided for determining whether a subject has a graft tolerant phenotype. In practicing the subject methods, the expression of at least one gene in a sample from the subject, e.g., a blood sample, is assayed to obtain an expression evaluation for the at least one gene. The obtained expression evaluation is then employed to determine whether the subject has a graft tolerant phenotype. Also provides are compositions, systems and kits that find use in practicing the subject methods. The methods and compositions find use in a variety of applications, including the determination of an immunosuppressive therapy regimen.

1 . A method of determining whether a subject has a graft tolerant phenotype, said method comprising:
 evaluating the expression of at least one gene, wherein said at least one gene comprises UHRF1, in a sample from said subject to determine whether said subject has a graft tolerant phenotype.   
     
     
         2 . The method according to  claim 1 , wherein said expression of at least one gene is evaluated by assaying said sample for a nucleic acid transcript of said gene. 
     
     
         3 . The method according to  claim 1 , wherein said expression of at least one gene is evaluated by assaying said sample for an expression product of said gene. 
     
     
         4 . The method according to  claim 1 , wherein said sample is a blood sample. 
     
     
         5 . The method according to  claim 4 , wherein said blood sample is a peripheral blood sample. 
     
     
         6 . The method according to  claim 1 , wherein the expression of said at least one gene, including UHRF1, from Tables 1, 2, 3 and/or 4 is evaluated. 
     
     
         7 . The method according to  claim 1 , wherein the method comprises:
 (a) obtaining an expression profile for said sample from said subject; and   (b) employing said obtained expression profile to determine whether said subject has a graft tolerant phenotype.   
     
     
         8 . The method according to  claim 7 , wherein said expression profile is compared to a reference expression profile in said employing step (b). 
     
     
         9 . The method according to  claim 7 , wherein said expression profile is determined using a microarray. 
     
     
         10 . A method of managing immunosuppressive therapy in a subject having a graft, said method comprising:
 (a) evaluating whether said subject has a graft tolerant phenotype according to  claim 1 ; and   (b) determining a future immunosuppressive therapy protocol based on said evaluating step (a) to manage immunosuppressive therapy in said subject.   
     
     
         11 . A system for determining whether a subject has a graft tolerant phenotype comprising:
 (a) a gene expression evaluation element for evaluating the expression of at least one gene, wherein said at least one gene comprises UHRF1, in a sample from said subject to obtain a gene expression result; and   (b) a phenotype determination element for employing said gene expression result to determine whether said subject has a graft tolerant phenotype.   
     
     
         12 . A reference expression profile for a phenotype that is one of:
 (a) graft tolerant; or   (b) graft intolerant;   
       wherein said expression profile is recorded on a computer readable medium. 
     
     
         13 . A collection of gene specific primers for evaluating gene expression, said collection comprising:
 primers specific for at least two of the genes, including UHRF1, of Tables 1, 2, 3 and/or 4.   
     
     
         14 . An array of probe nucleic acids immobilized on a solid support, said array comprising:
 a plurality of probe nucleic acid compositions, wherein each probe nucleic acid composition is specific for a gene whose expression profile is indicative of a graft tolerance, wherein at least two of said probe nucleic acid compositions correspond to genes listed in Tables 1, 2, 3 and/or 4.   
     
     
         15 . A kit comprising:
 (a) an array according to  claim 14 ; and   (b) a collection of gene specific primers according to  claim 13 .   
     
     
         16 . The method according to  claim 7 , wherein said expression profile comprises expression data for UHRF1. 
     
     
         17 . The method of  claim 7 , wherein said expression profile is determined using quantitative PCR. 
     
     
         18 . The method of  claim 1 , wherein at least five genes is evaluated. 
     
     
         19 . The system of  claim 11 , wherein at least five genes is evaluated. 
     
     
         20 . A kit for determining whether a subject has a graft tolerant phenotype, wherein the kit comprises:
 (a) gene expression evaluation element for evaluating the expression of at least one gene, wherein said at least one gene comprises UHRF1, in a sample from said subject to obtain a gene expression result; and   (b) a phenotype determination element for employing said gene expression result to determine whether said subject has a graft tolerant phenotype.   
     
     
         21 . The kit of  claim 20 , wherein at least five genes is evaluated.